1. Field of the Invention
The teachings provided herein relate to compositions comprising rutaecarpine derivatives that activate CYP1A2 through enzyme induction.
2. Description of Related Art
Caffeine is the world's most widely consumed psychoactive substance, but, unlike many other psychoactive substances, is legal and unregulated in nearly all jurisdictions. Beverages containing caffeine, such as coffee, tea, soft drinks, and energy drinks, enjoy great popularity. In North America, 90% of adults consume caffeine daily.
We spend approx ⅓ of our lives sleeping, and millions of Americans suffer from insomnia. The average adult, for example, should have 8 hours of sleep and usually gets about 6.9 hours of sleep. In 2005, the National sleep foundation survey showed about 75% of all adult Americans reported one or more symptoms of insomnia, and about 33% experienced insomnia almost every night. Caffeine consumption is suggested as significant contributor to the problem.
The problem of insomnia is addressed by several mechanisms in the current market. The mechanisms are generally directed to affecting the level of naturally-occurring neurotransmitters in a subject or stimulating/inhibiting the subject's response to certain neurotransmitters. Benzodiazepine, for example, is considered a first line treatment. Benzodiazepine (BDZ) works on the GABA receptor and improves sleep quality, but it can cause severe side-effects. Non-BDZ drugs promote sleepiness and cause less side-effects, but they can cause amnesia. Both BDZ and non-BDZ drugs carry a dependency risk. Examples include Eszopiclone (LUNESTA), flurazepam (DALMANE), and zolpidem (AMBIEN). Antidepressants are also used, including amitriptyline (ELAVIL), mirtazapine (REMERON), nefazodone (SERZONE), doxepin (ZONALON), and trazodone (DESYREL). Problems with the antidepressants include, but are not limited to, risk of use in the elderly, lack of understanding mode of action, sedation, dizziness, weight gain, and increased risk with cardiovascular disease and high blood pressure. Some over-the-counter medications have also been administered to treat insomnia, such as diphenhydramine. Problems with diphenhydramine include carry-over sedation (“hangover”) and tolerance effect. Other over-the-counter drugs that find such use include, but are not limited to, doxylamine, valerian root, and melatonin, where use is limited for at least the reasons of questionable effect and consistency. Other treatments include, for example, non-pharmacological methods of relaxation therapies, behavioral training, sleep hygiene, and stimulus control. Stimulus control (intake control) has been found to be the most effective behavioral intervention.
Pharmacological therapy shows some effectiveness but, as discussed above, several significant problems remain. Behavioral intervention has been shown to be the most effective treatment, but control over stimulant intake, particularly in the form of caffeine remains as a serious, representative compliance problem. About 228 million persons suffer from insomnia at some point throughout the year, and about 101 million persons suffer from insomnia every night. It is reasonably safe to assume that at least 90% of these populations consume caffeine. And, there is no current method of removing caffeine from the system of a subject, that is, caffeine that has already been ingested. As such, the population that has ingested caffeine still suffers an adenosine problem, where their adenosine level does not properly operate as a natural neurotransmitter due to the effect of the caffeine in their system.
Moreover, caffeine toxicity has become a rather serious problem that can result in significant, and possibly fatal, health conditions. Since RED BULL was launched in 1997, for example, energy drinks have become a multibillion dollar industry. More than 500 new products launched in 2006 alone, some of which may be labeled as an “energy supplement.” An example 16-ounce can contains two servings, each serving having 130 milligrams of caffeine; 1,000 mg of the organic acid taurine; 200 mg of the compound L-carnitine; 100 mg of inositol; and 50 mg of ginseng extract. The can warns that the drink is powerful and not recommended for children, pregnant women or people who are sensitive to caffeine. These drinks have caused seizures in healthy teenagers with otherwise no history of seizures. It is believed that ingesting too much of these drinks cause side-effects that can range from restlessness and headaches to tremors, confusion and seizures, addiction, and possibly even being fatal, causing irregular heartbeats and severe hypertension or death.
Accordingly, and for at least the above reasons, one of skill will appreciate a method of treating insomnia that carries less risk of side-effects, is more predictable in efficacy and, moreover, can remove caffeine that has already been ingested by the subject. The removal of the caffeine can act as an adenosine treatment, where the removal of caffeine from the system of the subject allows the adenosine to operate normally as a natural neurotransmitter. It should be appreciated that such a treatment can act to improve sleep, treat insomnia, as well as treat caffeine toxicity.